OBJECTIVES To determine whether the trajectory of preclinical lap time variability from a 400-m walk differentiates participants with future mild cognitive impairment (MCI)/Alzheimer's disease (AD) from matched controls. DESIGN A case-control retrospective study embedded in a large longitudinal cohort study, the Baltimore Longitudinal Study of Aging (BLSA). SETTING In the BLSA, participants were scheduled for clinical visits, including mobility and cognitive assessments. Data reported here were collected between April 2007 and September 2017 (average follow-up 5.2 ± 2.4 years). PARTICIPANTS 67 participants developed MCI/AD and 134 age- and sex-matched controls remained cognitively normal. MEASUREMENTS Diagnoses of MCI and AD were adjudicated at a consensus conference. The rate of change in lap time variability between MCI/AD cases prior to symptom onset and controls were compared using mixed effects linear regression, and adjusted for baseline executive function, memory, gait speed, and changes in gait speed. RESULTS Compared to controls, eventual MCI/AD cases had a greater rate of increase in lap time variability prior to symptom onset (β = 0.59, P = .009). This association was independent of baseline cognition, gait speeds at baseline or change over time from a 6-m or 400-m walk. CONCLUSION/IMPLICATIONS Independent of other early indicators and gait slowing, a greater rate of increase in lap time variability from a 400-m walk differentiates individuals who eventually develop MCI/AD from controls, suggesting that early pathology affects the automaticity of walking. Lap time variability can be assessed during routine clinical practice over time and might help identify individuals at risk for future MCI/AD.

中文翻译：

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400 米步行的单圈时间变化与未来的轻度认知障碍和阿尔茨海默病有关

目的 确定 400 米步行的临床前单圈时间变化轨迹是否能将未来轻度认知障碍 (MCI)/阿尔茨海默病 (AD) 的参与者与匹配的对照组区分开来。设计 一项纳入大型纵向队列研究——巴尔的摩老龄化纵向研究 (BLSA) 的病例对照回顾性研究。背景 在 BLSA 中，参与者被安排进行临床访问，包括活动能力和认知评估。此处报告的数据是在 2007 年 4 月至 2017 年 9 月期间收集的（平均随访时间为 5.2 ± 2.4 年）。参与者 67 名参与者发展为 MCI/AD，134 名年龄和性别匹配的对照组保持认知正常。测量 MCI 和 AD 的诊断在共识会议上作出裁决。使用混合效应线性回归比较症状出现前 MCI/AD 病例和对照之间单圈时间变异的变化率，并根据基线执行功能、记忆、步态速度和步态速度变化进行调整。结果 与对照组相比，最终的 MCI/AD 病例在症状出现前单圈时间变异性的增加率更高（β = 0.59，P = .009）。这种关联与基线认知、基线步态速度或 6 米或 400 米步行随时间的变化无关。结论/意义 独立于其他早期指标和步态减慢，400 米步行的单圈时间变异性增加的更大速率将最终发展为 MCI/AD 的个体与对照组区分开来，这表明早期病理会影响步行的自动性。